GAPVAC Phase I Trial in Newly Diagnosed Glioblastoma Patients
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|ClinicalTrials.gov Identifier: NCT02149225|
Recruitment Status : Active, not recruiting
First Posted : May 29, 2014
Last Update Posted : November 14, 2017
|Condition or disease||Intervention/treatment||Phase|
|Glioblastoma||Drug: APVAC1 vaccine plus Poly-ICLC and GM-CSF Drug: APVAC2 vaccine plus Poly-ICLC and GM-CSF||Phase 1|
This is a multicenter, open-label, single arm, first-in-man phase I trial to investigate the safety, feasibility and immunogenicity of the novel APVAC approach in patients with newly diagnosed GB.
- Safety: Determine the safety and tolerability profile of patient-tailored APVAC vaccines when administered with immunomodulators concurrent to maintenance temozolomide (TMZ) cycles.
- Feasibility: Determine duration and success rates for APVAC1 and APVAC2 processes and for vaccinations with APVAC drug products.
- Biological activity: Descriptive analysis of induced T-cell responses after vaccinations with APVAC1 and APVAC2 drug products plus immunomodulators.
Secondary Study Objectives:
- Identification of biomarkers putatively predictive for immunological response and/or associated with clinical success or failure. Analyzed biomarkers may include non-cellular parameters measured from tumor, plasma or serum, and cellular parameters measured from peripheral blood mononuclear cells (PBMCs), leukapheresis samples or isolated tumor-infiltrating lymphocytes (TILs).
- Description of potential clinical activity of the APVAC drug products. Descriptive analysis of clinical outcome in patients will be reported including OS and PFS. Correlation analysis of these parameters with immune response data may provide first hints on clinical activity of the vaccine.
After the standard chemoradiotherapy with TMZ has been completed and as soon as the start of the first maintenance TMZ cycle the vaccination phase begins. It starts with the first APVAC1 vaccination, followed by additional APVAC2 vaccinations at a later time point and ends with the Last Endpoint Evaluation Visit (LEEV) of a patient.
Single vaccinations with APVAC vaccines consist of an intradermal (i.d.) injection of the personalized APVAC drug product into the skin of the thigh, shoulder or abdomen followed by subcutaneous (s.c.) injection of 1.5 mg poly-ICLC (Hiltonol®) in close proximity to the vaccination site. The second immunomodulator GM-CSF (75 μg) will be applied i.d. to the APVAC vaccination site 10-30 min before injection of the APVACs.
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||16 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||A Phase I Trial of Actively Personalized Peptide Vaccinations Plus Immunomodulators in Patients With Newly Diagnosed Glioblastoma Concurrent to First Line Temozolomide Maintenance Therapy|
|Study Start Date :||October 2014|
|Estimated Primary Completion Date :||July 2018|
|Estimated Study Completion Date :||July 2018|
|Experimental: APVAC1 and 2 vaccine plus polyICLC and GMCSF concurrent to TMZ||
Drug: APVAC1 vaccine plus Poly-ICLC and GM-CSF
APVAC1 vaccines (i.d.) will be individually assembled for each patient and can be applied to the patient approx. 3 months after enrollment. APVAC1 drug products are composed of 5 to 10 peptides from the GAPVAC warehouse. The APVAC1 vaccine will be applied concurrent to maintenance TMZ cycles after completion of chemoradiation therapy (CRT). Beginning on day 15 of the first maintenance TMZ cycle, patients will receive 11 vaccinations with APVAC1 drug products during 22 weeks. 578 μg per peptide per vial are used.
Poly ICLC (1.5 mg s.c.) will be used as immunomodulator with all vaccinations except the second applications of APVAC1 (Day 2) and APVAC2 vaccines (Day 2*) to avoid dose accumulation on consecutive days.
The 2. immunomodulator GM-CSF (75 μg) will be applied i.d. with the first six vaccinations with both vaccines, APVAC1 and APVAC2. A total of 12 GM-CSF doses will be applied. GM-CSF will be applied to the APVAC vaccination site 10-30 min before injection of the APVACs.
Other Names:Drug: APVAC2 vaccine plus Poly-ICLC and GM-CSF
APVAC2 vaccines (i.d.) will be ready for use ca. 6 months after enrollment, as these peptides have to be newly synthesized for each patient following identification of the mutanome and corresponding mutated peptides in the HLA ligandome. APVAC2 drug products are composed of 1 or 2 peptides de novo synthesized for an individual patient. Patients will be repeatedly vaccinated with APVAC2 drug products beginning on day 15 of the 4. maintenance TMZ cycle. Patients will receive 8 vaccinations within 10 weeks. 578 μg per peptide per vial are used.
Poly-ICLC (1.5 mg s.c.) will be used as immunomodulator with all vaccinations except the second applications of APVAC1 (Day 2) and APVAC2 vaccines (Day 2*) to avoid dose accumulation on consecutive days.
GM-CSF (75 μg) will be applied i.d. with the first six vaccinations with both vaccines, APVAC1 and APVAC2. A total of 12 GM-CSF doses will be applied. GM-CSF will be applied to the APVAC vaccination site 10-30 min before injection of the APVACs.
- Safety profile of patient-tailored APVAC vaccines when administered with immunomodulators concurrent to maintenance TMZ cycles [ Time Frame: Continously for about 40 weeks plus follow-up ]Number of Adverse Events (AEs) and Serious Adverse Events (SAEs) and percentage of patients with AEs and SAEs (listed per grade and MedDRA (Medical Dictionary for Regulatory Activities ) preferred terms) will be reported.
- Frequency of CD8 T cells specific for vaccinated APVAC peptides as measure of immunological response to and biological activity of the vaccine [ Time Frame: Till 17 weeks of vaccination ]
To analyze whether vaccinations with APVAC drug products plus poly-ICLC and GM-CSF induce immune responses in the patients. Peripheral blood mononuclear cells will be analyzed for the presence and functionality of T cells recognizing the peptides vaccinated within the individualized APVACs.
- Immunogenicity rate: Number of vaccine induced T-cell responses normalized to the number of peptides vaccinated.
- Immune responder rate: Number of patients with at least one vaccine induced T-cell response
- Multi-TUMAP responder rate: Number of patients with at least two vaccine induced T-cell response
- Average number of immune responses per patient
- Frequency of immune cell populations in the blood and concentrations of a large panel of serum and plasma proteins with immunological relevance as a measure of the immune status of the patient [ Time Frame: Up to 10 months ]Putatively predictive for immunological response and/or associated with clinical success or failure. Analyzed biomarkers may include non-cellular parameters measured from tumor, plasma or serum, and cellular parameters measured from peripheral blood mononuclear cells (PBMCs), leukapheresis samples or isolated tumor-infiltrating lymphocytes (TILs).
- Overall survival [ Time Frame: 2018 (estimated) ]Median OS, the survival rate at one and at two years will be reported
- Progression-free survival [ Time Frame: At 6 months ]Median progression free survival (PFS) and PFS rates at 6 months will be described for patients in the safety and per protocol populations
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02149225
|Rigshospitalet, The Finsen Centre, Department of Oncology|
|Copenhagen, Denmark, 2100|
|Neurologische Klinik & Nationales Centrum für Tumorerkrankungen Heidelberg|
|Heidelberg, Germany, 69120|
|Zentrum für Neurologie und Klinik für Neurochirurgie|
|Tübingen, Germany, 72076|
|Leiden University Medical Center, Department of Medical Oncology|
|Leiden, Netherlands, 2333ZA|
|Vall d`Hebron University Hospital|
|Barcelona, Spain, 08035|
|Hôpitaux Universitaires de Genève|
|Geneva 14, Switzerland, 1211|
|Principal Investigator:||Wolfgang Wick, Professor||University of Heidelberg Medical Center|
|Principal Investigator:||Pierre-Yves Dietrich, Professor||Hôpitaux Universitaires de Genève|